Glyxambi is a once-daily oral tablet that combines empagliflozin (an SGLT2 inhibitor) with linagliptin (a DPP-4 inhibitor) for adults with type 2 diabetes. It offers an A1C reduction of around 1.0 to 1.5 percent along with cardiovascular and kidney benefits from empagliflozin, and is particularly useful when metformin is not tolerated or is contraindicated by chronic kidney disease, since linagliptin uniquely requires no renal dose adjustment.
What Glyxambi Contains
Glyxambi is co-marketed by Boehringer Ingelheim and Eli Lilly. Each tablet contains two complementary medications:
- Empagliflozin — an SGLT2 inhibitor that blocks reabsorption of filtered glucose in the proximal tubule of the kidney, allowing approximately 70 to 80 grams of glucose to be eliminated in urine each day. Effects include glucose lowering, body weight reduction of 2 to 4 kg, systolic blood pressure reduction of 3 to 5 mmHg, and demonstrated cardiovascular and kidney outcome benefits.
- Linagliptin — a DPP-4 inhibitor that prolongs the action of endogenous incretin hormones (GLP-1 and GIP), enhancing glucose-dependent insulin release and suppressing glucagon after meals. Linagliptin is unique among DPP-4 inhibitors in being primarily eliminated through bile rather than the kidney, requiring no dose adjustment in chronic kidney disease.
The combination targets two distinct physiological pathways — renal glucose excretion and the incretin axis — which makes the effects additive without significant overlap.
Available Strengths and Dosing
| Strength | Empagliflozin | Linagliptin | Use Case |
|---|---|---|---|
| 10/5 mg | 10 mg | 5 mg | Starting dose for most adults |
| 25/5 mg | 25 mg | 5 mg | Titration if A1C remains above goal after 8 to 12 weeks at 10/5 mg |
Dosing instructions:
- Take one tablet once daily in the morning, with or without food.
- If you miss a dose, take it as soon as remembered the same day; do not double the next dose.
- Maximum daily dose is one 25/5 mg tablet.
Who Glyxambi Is For
Glyxambi is approved for adults with type 2 diabetes as an adjunct to diet and exercise. Common scenarios in which it is chosen:
- A1C remains above goal despite metformin monotherapy, and the clinician prefers a single pill to add both classes
- Metformin is not tolerated (severe gastrointestinal side effects, B12 deficiency, lactic acidosis history) or is contraindicated by reduced eGFR
- Cardiovascular disease, heart failure, or chronic kidney disease makes empagliflozin’s outcome benefits desirable
- Weight gain from sulfonylureas or insulin needs to be offset
It is not approved for type 1 diabetes, diabetic ketoacidosis, or use in pediatric patients.
How Well It Works
Pivotal trials demonstrated:
- A1C reduction: approximately 1.1 percent for 10/5 mg and 1.2 to 1.5 percent for 25/5 mg, when added to background metformin, over 24 weeks.
- Weight loss: 2 to 3 kg over 24 to 52 weeks.
- Blood pressure: systolic reduction of 3 to 5 mmHg, useful for patients with concomitant hypertension.
- Cardiovascular benefit: EMPA-REG OUTCOME showed empagliflozin reduced cardiovascular death by 38 percent and heart failure hospitalization by 35 percent in patients with type 2 diabetes and established cardiovascular disease.
- Kidney protection: EMPA-KIDNEY demonstrated a 28 percent reduction in kidney disease progression in patients with chronic kidney disease.
- Linagliptin cardiovascular safety: CARMELINA trial established cardiovascular non-inferiority, with neutral effects on heart failure (unlike the saxagliptin SAVOR-TIMI 53 signal).
Side Effects
| Side Effect | Source Component | Frequency |
|---|---|---|
| Urinary tract infections | Empagliflozin | 7 to 9 percent |
| Genital yeast infections | Empagliflozin | 4 to 12 percent |
| Upper respiratory tract infection | Linagliptin | 6 to 7 percent |
| Nasopharyngitis | Linagliptin | 5 to 6 percent |
| Increased urination | Empagliflozin | 3 to 5 percent |
| Headache | Both | 3 to 5 percent |
| Hypoglycemia (when combined with insulin/sulfonylurea) | Both | Variable |
| Pancreatitis | Linagliptin | Rare (less than 0.5 percent) |
| Severe joint pain | Linagliptin (class effect) | Rare |
| Euglycemic DKA | Empagliflozin | Rare (less than 0.1 percent) |
| Volume depletion, hypotension | Empagliflozin | 1 to 3 percent |
| Acute kidney injury | Empagliflozin | Rare |
Warnings, Contraindications, and Precautions
- eGFR less than 30: empagliflozin is less effective at lowering glucose, though it may still be continued for cardiovascular and kidney benefits in some cases — discuss with your clinician.
- Type 1 diabetes: not approved.
- Active diabetic ketoacidosis or history of recurrent DKA: avoid.
- History of pancreatitis: use cautiously due to linagliptin.
- Severe hepatic impairment: use with caution.
- Heart failure: empagliflozin is beneficial; monitor fluid status during initiation.
- Hold around iodinated contrast and major surgery.
- Pregnancy: not recommended in second or third trimester.
Drug Interactions
- Strong CYP3A4 and P-gp inducers (rifampin, carbamazepine, phenytoin, St. John’s wort) can reduce linagliptin levels — combination is not recommended.
- Loop and thiazide diuretics increase volume depletion risk.
- Insulin and sulfonylureas increase hypoglycemia risk when combined; dose reduction may be needed.
- Lithium: SGLT2 inhibitors can alter lithium clearance — monitor levels.
Cost
Glyxambi typically retails for $600 to $750 per month at U.S. pharmacies. Manufacturer copay savings cards from Boehringer Ingelheim and Lilly can reduce eligible commercially insured patients’ out-of-pocket cost to $10 to $50 per month for up to 24 months. Medicare and Medicaid patients are not eligible for the savings card but may qualify for income-based patient assistance.
Storage and Handling
- Store at controlled room temperature, 68 to 77 degrees F.
- Keep in the original blister or bottle.
- Protect from moisture.
- Do not split, crush, or chew tablets.
Glyxambi vs Other Combinations
| Combination | Mechanisms | A1C Reduction | Renal-Friendly? |
|---|---|---|---|
| Glyxambi (empagliflozin + linagliptin) | SGLT2 + DPP-4 | 1.0 to 1.5% | Yes (linagliptin needs no renal dose adjustment) |
| Synjardy (empagliflozin + metformin) | SGLT2 + biguanide | 1.5 to 2.5% | No (metformin contraindicated below eGFR 30) |
| Trijardy XR (all three) | SGLT2 + DPP-4 + biguanide | 2.0 to 2.5% | Partial |
| Qtern (dapagliflozin + saxagliptin) | SGLT2 + DPP-4 | 1.0 to 1.5% | Yes, with caveats |
Glyxambi’s main niche is the patient who would benefit from SGLT2 + DPP-4 combination therapy but in whom metformin is not appropriate — typically chronic kidney disease with eGFR below 30, severe metformin intolerance, or after lactic acidosis. For everyone else, regimens that include metformin tend to be both cheaper and slightly more potent.
Place in Type 2 Diabetes Treatment
The ADA Standards of Care 2024 emphasize that the choice of second and third-line agents should be guided by patient factors, especially cardiovascular and kidney comorbidities. SGLT2 inhibitors are preferred when atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease is present; DPP-4 inhibitors are weight-neutral, low-risk add-ons. Combining both makes sense when both classes are needed and metformin is off the table. For an overview of the broader treatment landscape, see our guide on type 2 diabetes treatment options.
Practical Considerations for Patients
- Take Glyxambi at the same time each day to maintain steady plasma levels.
- Stay hydrated — drink at least 8 glasses of water daily to support kidney function and reduce dehydration risk from the SGLT2 component.
- Practice good genital hygiene to reduce yeast infection risk; uncircumcised men should clean the foreskin daily.
- Stop and call your clinician if you develop severe abdominal pain, persistent vomiting, fruity breath, or rapid breathing — symptoms of pancreatitis or DKA.
- Inform any new clinician (especially before surgery or contrast imaging) that you take Glyxambi.
- Discuss kidney function monitoring — eGFR should be checked at least annually, and more often in the first year of therapy.
Glyxambi in Prediabetes
Glyxambi is not approved for prediabetes. Lifestyle modification, metformin (off-label for high-risk individuals), and weight loss are the primary tools for preventing progression. See our guide on whether prediabetes is reversible for context on early intervention.
The Bottom Line
Glyxambi combines empagliflozin and linagliptin in one once-daily tablet, providing A1C reduction of 1.0 to 1.5 percent plus modest weight loss, blood pressure improvement, and the cardiovascular and kidney protection demonstrated by empagliflozin. Its main advantage is that linagliptin requires no renal dose adjustment, making the combination usable when metformin is contraindicated. Common side effects are genital yeast infections, urinary tract infections, and mild upper respiratory symptoms; rare but serious risks include pancreatitis, severe joint pain, and euglycemic DKA. Cost is similar to a single brand drug rather than two separate prescriptions thanks to manufacturer copay programs. Talk to your clinician about whether Glyxambi fits your kidney function, metformin tolerance, and overall diabetes plan.
